Clinical drug-resistant nodular sclerosing Hodgkin's lymphoma is associated with decreased bcl-2 expression in the surrounding lymphocytes and with increased bcl-2 expression in the Reed-Sternberg cells

Identification of patients with Hodgkin's lymphoma who are primary refractory to chemotherapy will have great impact on treatment planning. Several studies have indicated that up-regulation of the bcl-2 proto-oncogene expression in non-Hodgkin's lymphoma can cause resistance to chemotherapeutic drugs. For this reason we investigated the relationship between expression of bcl-2, the pro-apoptotic protein Bax and MIB-1 with clinical drug-resistance in Hodgkin's lymphoma. METHODS AND RESULTS: Seven patients with nodular sclerosis Hodgkin's lymphoma under 40 years of age, who failed to achieve complete remission upon primary chemotherapy and 10 matched patients who did achieve complete response were selected from the Eindhoven Cancer Registry. Tissue sections from both groups of patients were stained for bcl-2, Bax and MIB-1. In the non-responding patients Reed-Sternberg cells expressed bcl-2 more frequently using a cut-off point of <25% to indicate negative cells (P = 0.04), whereas no differences were observed in the expression of Bax and MIB-1. In non-responding patients the lymphocytes surrounding Reed-Sternberg cells expressed bcl-2 less frequently (P = 0.002), using a cut-off point of < 25%, whereas no difference was observed in the expression of Bax and MIB-1. CONCLUSION: A high percentage of Reed-Sternberg cells expressing bcl-2 protein and a low expression of bcl-2 proteifi in the surrounding lymphocytes is associated with treatment-failure, and subsequent poor survival in young patients with nodular sclerosing Hodgkin's lymphoma. These results need further validation in larger studies.